Background: Management of major life-threatening bleeding with factor Xa (FXa) inhibition poses complex challenges involving novel direct reversal agents competing with non-specific preexisting strategies. The recent availability of andexanet alfa (AA) led to a health-system guideline incorporating its use alongside the most commonly used historic agent, four-factor prothrombin complex concentrate (4F-PCC). Objectives: The objective was to characterize the use and efficacy of AA and 4F-PCC for reversal of FXa inhibition after implementation of the health-system guideline. Methods: This multi-hospital, retrospective cohort study included patients aged >18 years administered either AA or 4F-PCC between October 2018 to June 2020 with the indication for urgent reversal of FXa inhibitor-induced coagulopathy. The primary outcome assessed hemostatic efficacy between treatment groups. Secondary outcomes evaluated adjunct blood product administration, incidence of repeat pharmacologic reversal, incidence of thromboembolism, intensive care unit and hospital length of stays, and in-hospital mortality. Results: Eighty-five patients were included; 33 patients received AA and 52 patients received 4F-PCC. Effective hemostasis was achieved at similar rates in both treatment groups (84.8% vs 76.9%; P = .373). Thrombotic events occurring during the observed hospitalization were more frequent among the AA treated group (18% vs 3.8%, P = .027). No differences were observed for other secondary outcomes. Conclusion: Guideline use resulted in similar rates of effective hemostasis with a higher incidence of VTE in patients receiving AA. Further exploration with a larger, prospective study to evaluate these findings is warranted.

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